高级别浆液性卵巢癌中三级淋巴结构的活性受部位、基质和细胞相互作用的控制。
The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions.
发表日期：2024 Oct 08
作者：
Ian P MacFawn, Grant Magnon, Grace Gorecki, Sheryl Kunning, Rufiaat Rashid, Medard Ernest Kaiza, Huda Atiya, Ayana T Ruffin, Sarah Taylor, T Rinda Soong, Riyue Bao, Lan G Coffman, Tullia C Bruno
来源：
CANCER CELL
摘要：
大多数高级别浆液性卵巢癌 (HGSOC) 起源于输卵管，但会扩散到卵巢和腹膜腔，这凸显了了解 HGSOC 部位的抗肿瘤免疫的必要性。通过空间分析，我们发现与输卵管或大网膜肿瘤中的 TLS 相比，卵巢肿瘤内的三级淋巴结构 (TLS) 发育较差。我们揭示了一系列淋巴结构的转录差异，证明免疫细胞活性在存在于更发达的 TLS 中时会增加，并产生来自 HGSOC 肿瘤的预后、空间衍生的 TLS 特征。我们询问 TLS 邻近基质并评估正常间充质干细胞 MSC (nMSC) 如何支持 B 细胞功能和 TLS，这与癌症教育的 MSC (CA-MSC) 相反，后者否定了我们的 TLS 特征的预后益处，这表明致瘤基质可能会限制 TLS 的形成。版权所有 © 2024 Elsevier Inc. 保留所有权利。
Most high grade serous ovarian cancers (HGSOC) originate in the fallopian tube but spread to the ovary and peritoneal cavity, highlighting the need to understand antitumor immunity across HGSOC sites. Using spatial analyses, we discover that tertiary lymphoid structures (TLSs) within ovarian tumors are less developed compared with TLSs in fallopian tube or omental tumors. We reveal transcriptional differences across a spectrum of lymphoid structures, demonstrating that immune cell activity increases when residing in more developed TLSs and produce a prognostic, spatially derived TLS signature from HGSOC tumors. We interrogate TLS-adjacent stroma and assess how normal mesenchymal stem cells MSCs (nMSCs) may support B cell function and TLS, contrary to cancer-educated MSCs (CA-MSCs) which negate the prognostic benefit of our TLS signature, suggesting that pro-tumorigenic stroma could limit TLS formation.Copyright © 2024 Elsevier Inc. All rights reserved.